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Abstract Background Intravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity. Methods Patients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (

Abstract Background Although transcatheter aortic valve implantation (TAVI) is assumed to be a less invasive therapy in high-risk patients with aortic valve stenosis (AS), there have been limited data suggesting its beneficial effects on cardiovascular mortality in Japanese patients receiving dialysis therapy. Methods Hemodialysis patients with severe AS underwent either TAVI (n = 33) or surgical aortic valve replacement (SAVR, n = 25). We compared the postoperative outcomes and perioperative complications, including dialysis-associated parameters [e.g., intradialytic hypotension (IDH)], between TAVI and SAVR. Results A 30-day and 1-year mortality rate was nearly the same among the TAVI and the SAVR group. Incidence of permanent pacemaker implantation or other events, including stroke, bleeding and vascular complications, in the TAVI group were not different from those in SAVR patients during the 30-day or 1-year postoperative period. The incidence of IDH was increased following SAVR (odds ratio (OR) = 11.29 [95% CI 1.29–98.89]) but was not affected by TAVI (OR = 1.55 [95% CI 0.24–9.94]). Among the patients aged 75 or older, the incidence of IDH was particularly conspicuous in the SAVR group (OR = 15.75 [95% CI 2.30–107.93]). Because there were differences in background data (age, EuroSCORE II, and dialysis duration) between these groups, propensity score-matched analysis was conducted and showed no difference in the composite event-free probability between the TAVI and the SAVR group over one year (p = 0.816). Conclusions TAVI offers an alternative strategy to Japanese hemodialysis patients with severe AS, with nearly the same incidence of complications as SAVR during 1-year observation.

Abstract Background In nerve transfer for peripheral nerve injury, it is sometimes necessary to suture size-mismatched nerves. In 1993, a favorable suture method called the Ochiai suture method for size-mismatched nerve transfer was reported. However, there is currently a lack of substantial evidence beyond the original report. Therefore, this study aimed to verify the advantages of using the Ochiai suture method for size-mismatched nerve transfer. Methods A total of 18 rats were evaluated in this study and randomly divided into two groups. All rats underwent femoral to sciatic nerve transfer. Specifically, group A (n = 10) underwent the Ochiai suture method, while group B (n = 8) underwent the perineural suture method. After 12 weeks postoperatively, we conducted the sciatic functional index (SFI) test, measured muscle wet-weight, and performed histological evaluations. All data were compared between the two groups, with Welch’s t test for normally distributed data and Mann-Whitney's U test for non-normally distributed data. Statistical significance was set at p

Introduction Transient decrease in serum prostate‐specific antigen level can occur after abiraterone acetate withdrawal in male patient with metastatic castration‐resistant prostate cancer. Here, we report a case of abiraterone acetate withdrawal syndrome with transient prostate‐specific antigen decrease after progression to castration‐resistant disease while using upfront abiraterone therapy for high‐risk prostate cancer. Case presentation A 73‐year‐old man with hormone‐sensitive high‐risk prostate cancer with multiple bone metastases (prostate‐specific antigen level, 294.109 ng/mL) received upfront abiraterone/prednisolone combination and androgen deprivation therapy. One year later, prostate‐specific antigen level decreased to 0.017 ng/mL (nadir) but it gradually rose by 15 months after treatment initiation. He was diagnosed as castration‐resistant and new bone metastases appeared. After abiraterone was discontinued, prostate‐specific antigen level decreased and stabilized at a low level for 5 months. Conclusion Abiraterone acetate withdrawal syndrome was observed when hormone‐sensitive prostate cancer with upfront abiraterone therapy progressed to castration‐resistant prostate cancer.

Abstract Background The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. Methods Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. Discussion Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. Trial registration This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022–00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.

AIM: To establish a recording system with a direct view of the surgeon to supplement video recording under an operating microscope, which lacks information on the movement and position of the surgeon's hands, and to facilitate the reproduction of a skilled surgeon's technique by a surgeon in training. METHODS: A small camera was attached to the operating microscope with a custom adapter. Microscopic surgeon's view and direct surgeon's view through this new camera were recorded in the surgical recording system. Both movies were synchronized and analyzed how do surgeons handle the instruments. RESULTS: A small camera attached to the operating microscope allowed the surgeon's hands motion to be recorded without interfering with the surgeon's movements. Different surgeons used different methods to manipulate the ultrasound handpiece and the irrigation/aspiration device. Even in the simple paracentesis procedure, different surgeons used different methods. Surgeons-in-training were able to identify and improve their weaknesses by watching synchronized movies of their hand motions and microscopic view. CONCLUSION: Simultaneous recording the surgical field out of the operating microscopic view by a small camera set on the microscope is comprehensive and improves surgeons-in-training understanding and learning surgeries.

Abstract Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post‐operative survival outcomes. To test this hypothesis, we utilised a multi‐institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09–1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10–1.46). Compared to cases with 0–2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09–1.51) and 1.47 (95% CI, 1.22–1.78), respectively (ptrend

Abstract Purpose The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. Methods Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. Results The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2–590) in the cancer/dysplasia group and 48 (1–580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p

Abstract The short-lived radionuclide aluminium-26 (26Al) isotope is a major heat source for early planetary melting. The aluminium-26 – magnesium-26 (26Al-26Mg) decay system also serves as a high-resolution relative chronometer. In both cases, however, it is critical to establish whether 26Al was homogeneously or heterogeneously distributed throughout the solar nebula. Here we report a precise lead-207 – lead-206 (207Pb-206Pb) isotopic age of 4565.56 ± 0.12 million years (Ma) for the andesitic achondrite Erg Chech 002. Our analysis, in conjunction with published 26Al-26Mg data, reveals that the initial 26Al/27Al in the source material of this achondrite was notably higher than in various other well-preserved and precisely dated achondrites. Here we demonstrate that the current data clearly indicate spatial heterogeneity of 26Al by a factor of 3-4 in the precursor molecular cloud or the protoplanetary disk of the Solar System, likely associated with the late infall of stellar materials with freshly synthesized radionuclides.

Abstract The collapsing dynamics of relativistic fluid are explored in f(R) gravity in detailed systematic manner for the non-static spherically symmetric spacetime satisfying the equation of the conformal Killing vector. With quasi-homologous condition and diminishing complexity factor condition, exact solutions for dissipative as well as for non-dissipative system are found and the astrophysical applications of these exact solutions are discussed. Furthermore, it is demonstrated that $$f(R)=R,$$ f ( R ) = R , which is the extensive restriction of f(R) gravity, prior solutions of the collapsing fluid in general relativity, can be retrieved.

Abstract Background Mycobacterium obuense (M. obuense) is a rapidly growing mycobacterium (RGM) which has been considered nonpathogenic. Here, we report a case of disseminated non-tuberculous mycobacterial (NTM) infection caused by M. obuense in an immunocompromised patient. Case presentation A 16-year-old boy was referred to our hospital due to acute myeloid leukemia. During the treatment of leukemia, the patient exhibited continuous fever, and diffuse miliary nodules with random distribution were found on chest computed tomography. Repeated examinations of bacterial culture tests revealed sputum and urine samples to be smear-positive for acid-fast bacillus, and blood culture from a peripherally inserted central catheter line showed the growth of NTM. The NTM species was identified as M. obuense by mass spectrometry and confirmed by genome sequencing. Combination therapy with amikacin, rifampicin, azithromycin, and moxifloxacin significantly improved the patient’s symptoms and radiological findings. Conclusion We report a case of disseminated NTM infection caused by M. obuense for which combination anti-microbial therapy was effective. An immunocompromised host indwelling catheter is at risk of RGM bloodstream infections. Although relatively rare, M. obuense may be considered as a potential pathogen causing infectious diseases, especially in high-risk patients.

Abstract Adenosine triphosphate (ATP) is an extracellular signaling molecule that mainly affects the pathophysiological situation in the body and can be sensed by purinergic receptors, including ionotropic P2X7. Neuronal stem cells (NSCs) remain in adult neuronal tissues and can contribute to physiological processes via activation by evoked pathophysiological situations. In this study, we revealed that human-induced pluripotent stem cell-derived NSCs (iNSCs) have ATP-sensing ability primarily via the purinergic and ionotropic receptor P2X7. Next, to develop a machine learning (ML)-based screening system for food-derived neuronal effective substances and their effective doses, we collected ATP-triggered calcium responses of iNSCs pretreated with several substances and doses. Finally, we discovered that ML was performed using composite images, each containing nine waveform images, to achieve a better ML model (MLM) with higher precision. Our MLM can correctly sort subtle unidentified changes in waveforms produced by pretreated iNSCs with each substance and/or dose into the positive group, with common mRNA expression changes belonging to the gene ontology signatures.

Objectives: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. Methods: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models. Results: A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose (P=0.049) and RV IgG titers during the entire observation period (P=0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response. Conclusions: The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis.

The present study aims to analyze the performance characteristics of the biogas dry reforming process conducted in a membrane reactor using Ni/Cr catalysts and to compare these characteristics with those obtained using pure Ni catalysts. The effect of the pre-set reaction temperature, the molar ratio of CH4:CO2 and the pressure difference between the reaction chamber and the sweep chamber on the characteristics of biogas dry reforming is analyzed. In the present work, the molar ratio of the supplied CH4:CO2 is varied to 1.5:1, 1:1 and 1:1.5. In this case, CH4:CO2 = 1.5:1 simulates a biogas. The pressure difference between the reaction chamber and the sweep chamber is varied to 0 MPa, 0.010 MPa and 0.020 MPa. The reaction temperature is changed to 400 °C, 500 °C and 600 °C. It is revealed that the highest concentration of H2 is achieved using a Ni/Cr catalyst when the molar ratio of CH4:CO2 is 1.5:1 at the differential pressure of 0.010 MPa and the reaction temperature of 600 °C. Under this condition, the H2 yield, H2 selectivity and thermal efficiency are 12.8%, 17.5% and 174%, respectively. The concentration of the H2 produced using a Ni/Cr catalyst is larger than that produced using a Ni catalyst regardless of the pre-set reaction temperature, the molar ratio of CH4:CO2 and the differential pressure.

Abstract CRISPR genome editing is a powerful tool for elucidating biological functions. To modify the genome as intended, it is essential to understand the various modes of recombination that can occur. In this study, we report complex vector insertions that were identified during the generation of conditional alleles by CRISPR editing using microhomology-mediated end joining (MMEJ). The targeting vector contained two loxP sequences and flanking 40-bp microhomologies. The genomic regions corresponding to the loxP sequences were cleaved with Cas9 in mouse embryonic stem cells. PCR screening for targeted recombination revealed a high frequency of bands of a larger size than expected. Nanopore sequencing of these bands revealed complex vector insertions mediated not only by MMEJ but also by non-homologous end joining and homologous recombination in at least 17% of the clones. A new band appeared upon improving the PCR conditions, suggesting the presence of unintentionally modified alleles that escape standard PCR screening. This prompted us to characterize the recombination of each allele of the genome-edited clones using heterozygous single nucleotide polymorphisms, leading to confirmation of the presence of homozygous alleles. Our study indicates that careful quality control of genome-edited clones is needed to exclude complex, unintended, on-target vector insertion.

Abstract Mercury’s magnetosphere is known to involve fundamental processes releasing particles and energy like at Earth due to the solar wind interaction. The resulting cycle is however much faster and involves acceleration, transport, loss, and recycling of plasma. Direct experimental evidence for the roles of electrons during this cycle is however missing. Here we show that in-situ plasma observations obtained during BepiColombo’s first Mercury flyby reveal a compressed magnetosphere hosts of quasi-periodic fluctuations, including the original observation of dynamic phenomena in the post-midnight, southern magnetosphere. The energy-time dispersed electron enhancements support the occurrence of substorm-related, multiple, impulsive injections of electrons that ultimately precipitate onto its surface and induce X-ray fluorescence. These observations reveal that electron injections and subsequent energy-dependent drift now observed throughout Solar System is a universal mechanism that generates aurorae despite the differences in structure and dynamics of the planetary magnetospheres.

Abstract Background A population of regulatory T cells (Treg), which reside within thymic nurse cell complexes, express adiponectin and abrogate breast cancer development in transgenic mice. In this study, we examined whether adiponectin‐expressing Treg could impair triple‐negative breast cancer, which is defined by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor‐2. Methods CD4‐ and CD25‐positive cells were sorted from cultured T lymphocytes of a previously characterized experimental thymic tumor model composed of thymic nurse cells and abundant lymphoid stroma. These sorted cells were examined for FOXP3 and adiponectin immunoreactivity and subsequently exposed to triple‐negative breast cancer MDA‐MB‐157 and ‐231 cells. Results Adiponectin‐expressing Treg were obtained by CD4‐ and CD25‐positive sorting and cell death was induced in triple‐negative breast cancer cells through the cell‐in‐cell phenomenon. Conclusions Adiponectin‐expressing Treg may be candidates for adoptive cell therapy against triple‐negative breast cancer.

Objective:. To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG). Background:. A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown. Methods:. Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high cost and estimated the likelihood of RG to reduce overall cost under a Bayesian framework. All cost data were converted to ratios to the average cost of all operations performed at our center in year FY2021. Results:. We identified 119 patients who underwent gastrectomy. The incidence of postoperative complications (Clavien-Dindo >IIIa; RG, 10% vs OG, 13%) did not significantly differ between approaches. The median length of stay was 3 days shorter for RG versus OG (4 vs 7 days, P < 0.001). Intraoperative cost ratios were significantly higher for RG (RG, 2.6 vs OG, 1.7; P < 0.001). However, postoperative hospitalization cost ratios were significantly lower for RG (RG, 2.8 vs OG, 3.9; P < 0.001). Total perioperative cost ratios were similar between groups (RG, 6.1 vs OG, 6.4; P = 0.534). The multiple Bayesian generalized linear analysis showed RG had 76.5% posterior probability of overall perioperative cost reduction (adjusted risk ratio of 0.95; 95% credible interval, 0.85–1.07). Conclusions:. Despite increased intraoperative costs, total perioperative costs in the RG group were similar to those in the OG group because of reduced postoperative hospitalization costs.

Objective: Retinal vein occlusion (RVO) can lead to visual impairment, but the development of collateral vessels can sometimes mitigate significant damage. This study aimed to investigate the relationship between collateral vessels and hypertension, the most common underlying condition associated with RVO, by comparing spontaneously hypertensive rats (SHRs) and wild-type Wister rats (WWRs). We also examined the differences between WWRs and SHRs in terms of sphingosine 1-phosphate receptor 1 (S1PR1) expression and its product nitric oxide synthase 3 (NOS3) expression, which are involved in the formation of collateral vessels after vascular occlusion. Methods: Laser photocoagulation (PC) was used to occlude one randomly selected retinal vein in WWRs and SHRs, and the area surrounding the occluded vessel was examined using optical coherence tomography angiography. If reperfusion of the occluded vessel occurred within 2 weeks, the vessel was re-occluded repeatedly by PC. The number of eyes with successfully occluded vessels accompanied by collateral vessels was recorded. Then, WWRs and SHRs were divided into the following four groups: 1) control (no treatment), 2) vehicle (20% DMSO), 3) S1PR1 agonist (2 mg/mL SEW2871), and 4) S1PR1 antagonist (0.25 mg/mL VPC 23019) groups. The drugs were administered intravitreally in all groups except the control. The number of laser shots required for successful RVO was recorded. Histological evaluation and quantitative real-time PCR of S1PR1 and NOS3 were performed to elucidate the mechanisms underlying collateral vessel formation. Results: The proportion of eyes achieving successful vein occlusion was lower in SHRs (4/12 eyes, 33.3%) than in WWRs (8/10 eyes, 80%, p = 0.043). NOS3 expression at 6 h after PC was significantly higher in WWRs than in SHRs (p = 0.021). In WWRs treated with SEW2871, vein occlusion failed in 7 of 10 eyes (70%). The expression of NOS3 was significantly higher in the SEW2871 treatment group than in the untreated group (p

Abstract The spin Hall effect enables fast and reliable writing operations for next‐generation spin‐orbit‐torque magnetoresistive random‐access memories (SOT‐MRAMs). To develop SOT‐MRAMs; however, the spin Hall material should have a sufficiently low writing energy and high annealing stability for the semiconductor integration process. Thus far, none of the crystalline‐based spin Hall materials are able to satisfy these requirements. Here, a promising solution for SOT‐MRAMs is provided using amorphous W─Ta─B alloys. Even without a long‐range crystal order, W─Ta─B alloys exhibit both large effective spin Hall angles up to 40% derived from a Ta substitutional doping and superior annealing stability (up to 400 °C) due to the addition of B, enabling them to satisfy both requirements. Nanoscale three‐terminal SOT‐MRAM cells are fabricated, and these are demonstrated to have high magnetoresistance ratios (up to 130%) and extremely low intrinsic switching current densities (down to 4 × 106 A cm−2). These results show that amorphous spin Hall materials can provide the key for realizing high‐performance SOT‐MRAMs.

Wickerhamiella is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples usually only contain three species: W. infanticola, W. pararugosa and W. sorbophila. In this study, we isolated W. tropicalis from a blood sample of a six-year-old female with a history of B-cell precursor lymphoblastic leukemia in Japan in 2022. Though the strain was morphologically identified as Candida species by routine microbiological examinations, it was subsequently identified as W. tropicalis by sequencing the internal transcribed spacer (ITS) of ribosomal DNA (rDNA). The isolate had amino acid substitutions in ERG11 and FKS1 associated with azole and echinocandin resistance, respectively, in Candida species and showed intermediate-resistant to fluconazole and micafungin. The patient was successfully treated with micafungin. Furthermore, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) detected three novel peaks that are specific for W. tropicalis, indicating that MALDI-MS analysis is useful for rapid detection of Wickerhamiella species in routine microbiological examinations.

3-Methylglutaconic aciduria type 1 (MGCA1) is an inborn error of leucine catabolism caused by pathogenic variants of the AUH gene. MGCA1 can be identified by newborn screening (NBS) with elevated C5-OH levels. We herein report a girl with MGCA1 detected by NBS. On day 5 after birth, NBS detected high C5-OH levels of 1.17 μmol/L (1.56 μmol/L [retest]). A urinary organic acid analysis revealed the abnormal excretion of 3-methylglutaconic, 3-methylglutaric, and 3-hydroxyisovaleric acids. Two novel heterozygous loss-of-function variants in the AUH gene were identified by genetic testing. We observed the patient without any treatment, such as a leucine-restricted diet. She had episodes of febrile illness several times in infancy but did not develop febrile convulsions or encephalopathy. She is now two years and six months old, and her physical growth and psychomotor development have progressed normally. In a review of the literature and our case, four children with MGCA1 identified during the neonatal period were asymptomatic or exhibited speech delay, regardless of whether or not they had been managed with specific treatments. Treatments such as dietary leucine restriction and carnitine supplementation may have little effect on MGCA1 in childhood; however, further investigation is warranted to evaluate the benefits of specific treatments to prevent potential long-term neurological complications.

Abstract A 73‐year‐old woman with lung adenocarcinoma (cT4N3M1a: Stage IVA) was treated with atezolizumab as the eighth line of therapy. Four weeks after the fourth dose of atezolizumab, the prothrombin time (PT) and activated thromboplastin time (APTT) were prolonged. Coagulation factor V (FV) activity was decreased, and FV inhibitors were observed. There was no history of PT or APTT prolongation or bleeding before the use of atezolizumab. Atezolizumab‐induced coagulation FV inhibitor was diagnosed. After 2 weeks, the PT and APTT spontaneously normalized. FV activity improved and the FV inhibitors disappeared after 6 and 9 weeks, respectively.

IntroductionIndividuals with Autism Spectrum Disorder (ASD) show atypical recognition of facial emotions, which has been suggested to stem from arousal and attention allocation. Recent studies have focused on the ability to perceive an average expression from multiple spatially different expressions. This study investigated the effect of autistic traits on temporal ensemble, that is, the perception of the average expression from multiple changing expressions.MethodsWe conducted a simplified temporal-ensemble task and analyzed behavioral responses, pupil size, and viewing times for eyes of a face. Participants with and without diagnosis of ASD viewed serial presentations of facial expressions that randomly switched between emotional and neutral. The temporal ratio of the emotional expressions was manipulated. The participants estimated the intensity of the facial emotions for the overall presentation.ResultsWe obtained three major results: (a) many participants with ASD were less susceptible to the ratio of anger expression for temporal ensembles, (b) they produced significantly greater pupil size for angry expressions (within-participants comparison) and smaller pupil size for sad expressions (between-groups comparison), and (c) pupil size and viewing time to eyes were not correlated with the temporal ensemble.DiscussionThese results suggest atypical temporal integration of anger expression and arousal characteristics in individuals with ASD; however, the atypical integration is not fully explained by arousal or attentional allocation.

Although meeting close friends through video calls has become common, less is known about its stress-buffering effect. This study aims to examine whether cardiovascular responses to stress are decreased when the presence of a friend on a monitor compared to the presence of a friend in person or alone. Forty-six undergraduate students completed a stress task while in the room with a friend (1) in person (in-person condition), (2) on Zoom (online condition), or (3) alone (alone condition). Blood pressure and heart rate were monitored throughout the experiment. Analyses revealed that diastolic blood pressure after the stress was recovered closer to the pre-stress state under in-person and online conditions than alone condition. However, the study observed no differences across groups regarding self-reported affect. In summary, this result suggests that even the online presence of a friend, as well as in-person friends, may help recover blood pressure to the original state without one's awareness.

Background and aimUstekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment.Materials and methodsWe retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment.ResultsOf the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48.ConclusionsThe baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Purpose. The microenvironment is required for tissues to maintain their properties in vivo. This microenvironment encompasses the types and three-dimensional arrangement of cells forming the tissues, and their interactions with neighboring cells and extracellular matrices, as represented by the stem cell niche. Tissue regeneration depends not on the original tissue source of the transplanted cells, but on the microenvironment in which they are transplanted. We have previously reported pulp regeneration in a heterotopic root graft model by transplantation of conditioned medium alone, which suggests that host-derived cells expressing receptors for migration factors in conditioned medium migrate into the root canal and cause pulp regeneration. Regenerative medicine is needed to restore the original function of complex tissues. To achieve this, it is necessary to reproduce the changes in the microenvironment of the host tissue that accompany the regenerative response. Therefore, it is important to reproduce the microenvironment in vivo for further development of tissue regeneration therapy. Periostin is also found in the epithelial–mesenchymal junction, with expression sites that differ depending on the mineralized matrix stage, and is involved in regulation of calcification. Methods. We investigate whether periostin contributes to microenvironmental changes in regenerated pulp tissue. Dental pulp stem cells were induced into dentin, and gene expression of DSPP, nestin, DMP1, Runx2, and periostin was analyzed by qPCR and protein expression by IHC. Similarly, gene expression was analyzed using qPCR and protein expression using IHC in regenerated dental pulp obtained by ectopic transplantation. Results. Since these regenerated tissues were observable on the same slice, it was possible to understand changes in the microenvironment within the tissues. Conclusions. Periostin promoted proliferation of pulp stem cells, migration in type I collagen, and calcification in regenerated pulp, which strongly suggests that periostin is a promising candidate as a factor that contributes to the microenvironment of regenerated pulp.

Introduction Malignancy during pregnancy requires consideration of both the mother and fetus. We report a patient with renal cell carcinoma during pregnancy who was treated with robot‐assisted partial nephrectomy. Case presentation The patient was incidentally found to have a renal mass on abdominal ultrasonography. Definitive diagnosis of cT1aN0M0 RCC was made by enhanced computed tomography. Subsequently, pregnancy was discovered. RAPN was performed without complications. Pathologic examination revealed clear cell RCC. There were no postoperative complications, and the baby was born safely. Conclusion RAPN can be safe and effective even during pregnancy. Every pregnant patient requires individualized treatment involving the timing of surgery, the procedure used, and management based on the condition of the mother and fetus, tumor stage, and the experience of the surgical team.

Abstract Chorus waves are naturally occurring electromagnetic emissions in space and are known to produce highly energetic electrons in the hazardous radiation belt. The characteristic feature of chorus is its fast frequency chirping, whose mechanism remains a long-standing problem. While many theories agree on its nonlinear nature, they differ on whether or how the background magnetic field inhomogeneity plays a key role. Here, using observations of chorus at Mars and Earth, we report direct evidence showing that the chorus chirping rate is consistently related to the background magnetic field inhomogeneity, despite orders of magnitude difference in a key parameter quantifying the inhomogeneity at the two planets. Our results show an extreme test of a recently proposed chorus generation model and confirm the connection between the chirping rate and magnetic field inhomogeneity, opening the door to controlled plasma wave excitation in the laboratory and space.

Objectives: To establish a point-of-care test for coronavirus disease 2019 (COVID-19), we developed a dry loop-mediated isothermal amplification (LAMP) method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Methods: We carried out reverse transcription (RT)-LAMP using the Loopamp SARS-CoV-2 Detection kit (Eiken Chemical, Tokyo, Japan). The entire mixture, except for the primers, is dried and immobilized inside the tube lid. Results: To determine the specificity of the kit, 22 viruses associated with respiratory infections, including SARS-CoV-2, were tested. The sensitivity of this assay, determined by either a real-time turbidity assay or colorimetric change of the reaction mixture, as evaluated by the naked eye or under illumination with ultraviolet light, was 10 copies/reaction. No LAMP product was detected in reactions performed with RNA from any pathogens other than SARS-CoV-2. After completing an initial validation analysis, we analyzed 24 nasopharyngeal swab specimens collected from patients suspected to have COVID-19. Of the 24 samples, 19 (79.2%) were determined by real-time RT-PCR analysis as being positive for SARS-CoV-2 RNA. Using the Loopamp SARS-CoV-2 Detection kit, we detected SARS-CoV-2 RNA in 15 (62.5%) of the 24 samples. Thus, the sensitivity, specificity, positive predictive value, and negative predictive values of the Loopamp 2019-CoV-2 detection reagent kit were 78.9%, 100%, 100%, and 55.6%, respectively. Conclusions: The dry LAMP method for detecting SARS-CoV-2 RNA is fast and easy to use, and its reagents can be stored at 4°C, solving the cold chain problem; thus, it represents a promising tool for COVID-19 diagnosis in developing countries.

Objectives: Fetal human cytomegalovirus (HCMV) infection might be involved in fetal growth restriction (FGR). Maternal serostatus and the prevalence of congenital HCMV infection are affected by various factors, such as socioeconomic status and ethnicity. Therefore, the prevalence of congenital HCMV-related FGR should be examined in each region. Methods: Seventy-eight cases of FGR with delivery between January 2012 and January 2017 at Fujita Health University Hospital were studied. Twenty-one non-FGR cases were also included as a control group. Placental sections obtained from the FGR and control cases were immunostained with two primary antibodies for detecting immediate early antigens. Results: Nineteen placental samples from FGR cases with another etiology were excluded. Finally, 59 placental samples from FGR cases of unknown etiology were included in the pathological analysis. Four of 59 (6.8%) placental samples were positive for HCMV antigen. All four positive cases were stained with the M0854 antibody, and there were no positive case with the MAB810R antibody. Neither maternal nor infantile clinical features were different between the HCMV-positive and -negative FGR cases. A pathological examination showed a hematoma in three of four cases and infarction in two of four cases. Conclusions: HCMV antigen was detected in 6.8% of placental samples obtained from FGR cases without an obvious etiology. No remarkable maternal or neonatal clinical features discriminated HCMV-related FGR from FGR due to other causes. Vasculitis and inflammation might play important roles in the pathogenesis of HCMV-related FGR.

Abstract Background In patients with Fontan circulation, hemorrhage can cause life-threatening circulatory collapse, since Fontan circulation strongly depends on the preload. Furthermore, parturients with placenta accreta spectrum are at a high risk of rapid and massive hemorrhage. Herein, we report the case of an intra-aortic balloon occlusion used for a Fontan-palliated parturient with placenta increta with successful anesthetic management. Case presentation A 35-year-old-female with Fontan circulation diagnosed with placenta increta underwent a cesarean hysterectomy. The main goal during anesthetic management was to maintain sufficient preload. Infrarenal intra-aortic balloon occlusion was used to reduce intraoperative hemorrhage. The hemodynamic changes caused were well tolerated in this case. Conclusions Intra-aortic balloon occlusion was used in a Fontan-palliated parturient with placenta increta with successful anesthetic management.

Using laser speckle flowgraphy (LSFG), we investigated the time course of changes in choroidal circulation hemodynamics after a cold pressor test in healthy eyes. This prospective study included the right eye of 19 young healthy participants. The macular mean blur rate (MBR) was measured with LSFG. The MBR, intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), mean blood pressure (MBP), and ocular perfusion pressure (OPP) were evaluated at baseline; immediately after the test and 10, 20, and 30 min later. Immediately after the test (0 min), SBP, DBP, MBP, and OPP were significantly elevated compared with those at baseline. The macular MBR significantly increased by +10.3 ± 7.1% immediately after the test. However, there was no change after 10, 20, and 30 min in the above parameter. A significant positive correlation of the macular MBR with the SBP, MBP, and OPP was observed. In young healthy individuals, increased sympathetic activity induced by a cold pressor test increases choroidal hemodynamics in the macula along with an increase in systemic circulatory dynamics, which normalizes after 10 min. Therefore, LSFG may provide a novel approach for assessing sympathetic activity and intrinsic vascular responsiveness in the eye.

Abstract Teicoplanin, a glycopeptide antimicrobial, is recommended for therapeutic drug monitoring, but it remains unclear how to target the area under the concentration‐time curve (AUC). This simulation study purposed to demonstrate the potential of the Bayesian forecasting approach for the rapid achievement of the target AUC for teicoplanin. We generated concordant and discordant virtual populations against a Japanese population pharmacokinetic model. The predictive performance of the Bayesian posterior AUC in limited sampling on the first day against the reference AUC was evaluated as an acceptable target AUC ratio within the range of 0.8–1.2. In the concordant population, the probability for the maximum a priori or Bayesian posterior AUC on the first day (AUC0–24) was 61.3% or more than 77.0%, respectively. The Bayesian posterior AUC on the second day (AUC24–48) was more than 75.1%. In the discordant population, the probability for the maximum a priori or Bayesian posterior AUC0–24 was 15.5% or 11.7–80.7%, respectively. The probability for the maximum a priori or Bayesian posterior AUC24–48 was 23.4%, 30.2–82.1%. The AUC at steady‐state (AUCSS) was correlated with trough concentration at steady‐state, with a coefficient of determination of 0.930; the coefficients on days 7 and 4 were 0.442 and 0.125, respectively. In conclusion, this study demonstrated that early sampling could improve the probability of AUC0–24 and AUC24–48 but did not adequately predict AUCSS. Further studies are necessary to apply early sampling‐based model‐informed precision dosing in the clinical settings.

Abstract The station coordinates derived from GNSS (Global Navigation Satellite System) with a conventional static method underpin the study of Earth and planetary science and surveying and mapping. For the continuous provision of high-quality coordinates, it is mandatory to cope with the increasing deviation from the global standard reference frame and the launch of modern GPS (Global Positioning System) satellites. To provide coordinates agreed with ITRF2014 (International Terrestrial Reference Frame 2014) at several millimeters for GEONET (GNSS Earth Observation Network System) in Japan, we developed a new analysis strategy named F5 and assessed the reprocessed station coordinates from 1996. The major updates in F5 can be summarized as incorporating global network processing and enhancements in troposphere modeling. As for the troposphere enhancements, a modern mapping function VMF1 (Vienna Mapping Functions 1) was employed and time intervals for troposphere estimates were shortened. Station coordinates in the global network showed a great agreement with ITRF2014 at several millimeters in the recent 20 years and comparable or slightly better performance with IGS (International GNSS Services) Analysis Centers. The RMS (root mean square) averaged over all GEONET stations indicated very high accuracy of 3.2 mm (horizontal) and 7.3 mm (vertical); the latter accounts for an improvement of roughly 10% from the previous strategy. Sensitivity tests about troposphere estimates revealed that the reduced RMS was completely due to the short time intervals, not the use of VMF1, which contributed to partly suppressing the spurious vertical annual deformation. These results confirm that F5 is sufficiently accurate for the requirements of individual applications and infer the capability of detecting smaller signals the previous strategy could not resolve. Graphical Abstract